Genetic Basis of Candida Biofilm Resistance Due to Drug‐Sequestering Matrix Glucan
Open accessAbstract
Medical devices provide an ecological niche for microbes to flourish as a biofilm community, protected from antimicrobials and host defenses. Biofilms formed by Candida albicans, the most common fungal pathogen, survive exposure to extraordinarily high drug concentrations. Here, we show that beta-glucan synthase Fks1p produces glucan, which is deposited in the biofilm matrix. The extracellular glucan is required for biofilm resistance and acts by sequestering antifungals, rendering cells resistant to their action. These findings provide the genetic basis for how biofilm matrix production governs drug resistance by impeding drug diffusion and also identify a useful biofilm drug target.
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Fluconazole-resistant C. albicans may exhibit higher levels of β-glucans compared to susceptible strains.
“Few studies have shown that fluconazole-resistant (FR) C. albicans may also exhibit higher levels of β-glucans compared to susceptible strains (12, 16).”
From <i>Candida albicans</i> enhances iron uptake to maintain fluconazole resistance (2025) · cites this paper as [16]
The Results (page unavailable) report that fluconazole-resistant reference-strain biofilms had more β-1,3-glucan than the more susceptible FKS1-mutant biofilms. This supports the comparison in biofilms, but the paper does not establish that fluconazole-resistant C. albicans strains generally have higher β-glucan levels; it reports identical planktonic fluconazole susceptibility for the reference and FKS1/fks1Δ strains. (LLM, conf=0.88)
Experimental — accuracy not yet measuredGlucan synthesis has been associated with C. albicans biofilm resistance to azoles.
“Besides membrane sterols, cell wall glucans also affect fluconazole susceptibility, and glucan synthesis has been associated with C. albicans biofilm resistance to azoles (16).”
From <i>Candida albicans</i> enhances iron uptake to maintain fluconazole resistance (2025) · cites this paper as [16]
Secreted extracellular matrix acts as a physical barrier to drug penetration and contributes to structural integrity of biofilm.
“Biofilm drug resistance may also be attributed to the secreted extracellular matrix, which acts as a physical barrier to drug penetration and thereby directly contributes to the structural integrity of the biofilm.”
From Molecular and genetic basis of azole antifungal resistance in the opportunistic pathogenic fungus<i>Candida albicans</i> (2020) · cites this paper as [178]
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Self-citation
- Authors
- Nett, J. E., Sanchez, H., Cain, M. T., & Andes, D. R.
- Affiliations
- University of Wisconsin–Madison (US)
- Corresponding author
- Andes, David R.
- Venue
- The Journal of Infectious Diseases
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-07
- Volume
- 202
- Issue
- 1
- Pages
- 171-175
- ISSN
- 0022-1899 (ISSN-L)
- 1537-6613
- PMC
- PMC2880631
- OpenAlex
- W2124954220
- Cited by
- 250
- References
- 16
- Citations by year
- 2026: 7 · 2025: 16 · 2024: 5 · 2023: 15 · 2022: 10 · 2021: 14 · 2020: 13 · 2019: 12 · 2018: 16 · 2017: 23 · 2016: 20 · 2015: 23 · 2014: 18 · 2013: 16 · 2012: 15
- FWCI
- 11.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Infectious Diseases (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (T32HL007899)
- National Institute of Allergy and Infectious Diseases (R01AI073289)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
- Keywords
- Candida albicans, biofilm, antifungal resistance, β-glucan, beta-glucan synthase, drug sequestration, device-related infection, biofilm matrix, drug diffusion
- MeSH terms
- Animals, Antifungal Agents, Candida, Candidiasis, Dose-Response Relationship, Drug, Fungal Proteins, Glucans, Fluconazole, Gene Expression Regulation, Fungal, Biofilms, Drug Resistance, Fungal, Mice, Rats
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